RIPPLY2 p.Ser117=
c.351C>T · rs190833679 · VCV1549025
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0335%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.59 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 10.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0335%
Middle Eastern · 2/5,976 alleles
Filtering AF
0.0204%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0196%
Overall
0.0191%
302/1,580,168 alleles · ultra-rare
exomes 277/1,428,222 · genomes 25/151,946 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0335% | 2,988 |
| Admixed American | 0.025% | 4,005 |
| European (non-Finnish) | 0.0227% | 4,410 |
| South Asian | 0.0132% | 7,603 |
| Remaining individualsnot grpmax-eligible | 0.0131% | 7,621 |
| African / African-American | 0.00274% | 36,525 |
| Finnishnot grpmax-eligible | 0.00158% | 63,426 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- RIPPLY2
- Protein
- p.Ser117=
- Coding
- c.351C>T
- MANE Select
- NM_001009994
- dbSNP
- rs190833679
- Type
- single nucleotide variant
- Location
- chr6:83857353 (GRCh38)
- Gene constraint
- LOEUF 1.76 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.67
- Residue 117
- a UniProt-annotated variant site (in scdo6; likely pathogenic)
Similar variants
- RIPPLY2 p.Ala14Ser Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Ala14Thr Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Ala34Thr Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Glu118Lys Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Gly9Cys Uncertain significance ★★ ⚠ same type
- RIPPLY2 p.Met59Thr Uncertain significance ★★ ⚠ same type
- RIPPLY2 c.175-19C>T Likely benign ★★ same type
- RIPPLY2 p.Ala4= Benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ripply2-p-ser117 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown